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Extending kinome coverage by analysis of kinase inhibitor broad profiling data.
- Source :
-
Drug discovery today [Drug Discov Today] 2015 Jun; Vol. 20 (6), pp. 652-8. Date of Electronic Publication: 2015 Jan 14. - Publication Year :
- 2015
-
Abstract
- The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the relation between hit confirmation rates and inhibitor selectivity showed unexpectedly that higher selectivity can increase the likelihood of false positives. Third, comparing the coverage of a focused to that of a random library showed that the design based on a maximum number of scaffolds was superior to a limited number of scaffolds. Therefore, selective compounds can be used in target validation, enable the jumpstarting of new kinase drug discovery projects, and chart new biological space via phenotypic screening.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Databases, Protein
High-Throughput Screening Assays
Humans
Molecular Structure
Molecular Targeted Therapy
Protein Kinase Inhibitors chemistry
Protein Kinases genetics
Signal Transduction drug effects
Small Molecule Libraries
Structure-Activity Relationship
Workflow
Drug Discovery methods
Protein Kinase Inhibitors pharmacology
Protein Kinases metabolism
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5832
- Volume :
- 20
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Drug discovery today
- Publication Type :
- Academic Journal
- Accession number :
- 25596550
- Full Text :
- https://doi.org/10.1016/j.drudis.2015.01.002